Controlling Inflammation

Using short snippets of RNA to turn off a specific gene in certain immune cells, MIT researchers have shown that they can reduce the inflammation responsible for diseases such as atherosclerosis, other forms of heart disease, and some cancers.

Inflammation, one of the body’s defenses against disease and injury, helps wounds and infections heal, but too much inflammation can damage tissues. When fat and cholesterol build up on artery walls, for example, they produce inflammation that leads to atherosclerosis, a hardening of the arteries.

The MIT researchers’ technique for curbing inflammation relies on RNA interference, which disrupts the flow of genetic information from a cell’s nucleus to its protein-­building machinery. The key to successful RNA interference is finding a safe and effective way to deliver short strands of RNA that can bind with and destroy messenger RNA, which carries instructions from the nucleus.

In a recent study published in Nature Biotechnology, the researchers delivered short strands of RNA that turn down the inflammation response by blocking activity of a specific gene in white blood cells called monocytes. Packaged in nanoparticles made from a layer of fatlike molecules called ­lipidoids, the RNA successfully reduced inflammation in mice, without side effects.

The RNA snippets targeted the gene for the CCR2 receptor, a protein on the surface of monocytes. Without this receptor, monocytes cannot receive the signals they need to travel to the injury site and cause inflammation. Mice treated with this type of RNA showed much lower levels of inflammation in atherosclerosis, cancer, and recovery from heart attack.

Study authors Daniel Anderson and ­Robert Langer, ScD ‘74, both faculty members in MIT’s David H. Koch Institute for Integrative Cancer Research, have developed similar nanoparticles to deliver RNA interference treatments for other diseases, including liver and ovarian cancers. “These kinds of approaches have a lot of potential for many different diseases,” Anderson says.